RT Journal Article
SR Electronic
T1 DHX15 regulates CMTR1-dependent gene expression and cell proliferation
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201800092
DO 10.26508/lsa.201800092
VO 1
IS 3
A1 Francisco Inesta-Vaquera
A1 Viduth K Chaugule
A1 Alison Galloway
A1 Laurel Chandler
A1 Alejandro Rojas-Fernandez
A1 Simone Weidlich
A1 Mark Peggie
A1 Victoria H Cowling
YR 2018
UL https://www.life-science-alliance.org/content/1/3/e201800092.abstract
AB CMTR1 contributes to mRNA cap formation by methylating the first transcribed nucleotide ribose at the O-2 position. mRNA cap O-2 methylation has roles in mRNA stabilisation and translation, and self-RNA tolerance in innate immunity. We report that CMTR1 is recruited to serine-5–phosphorylated RNA Pol II C-terminal domain, early in transcription. We isolated CMTR1 in a complex with DHX15, an RNA helicase functioning in splicing and ribosome biogenesis, and characterised it as a regulator of CMTR1. When DHX15 is bound, CMTR1 activity is repressed and the methyltransferase does not bind to RNA pol II. Conversely, CMTR1 activates DHX15 helicase activity, which is likely to impact several nuclear functions. In HCC1806 breast carcinoma cell line, the DHX15–CMTR1 interaction controls ribosome loading of a subset of mRNAs and regulates cell proliferation. The impact of the CMTR1–DHX15 interaction is complex and will depend on the relative expression of these enzymes and their interactors, and the cellular dependency on different RNA processing pathways.